Allergies are among the most common health problems affecting the life of patients of all age. Allergic diseases are nowadays recognized as an epidemic by the World Health Organization (WHO). The prevalence of allergies has been shown to increase in the past decades. Modern life style, especially urban, has been associated with high prevalence and higher severity of allergic manifestations.
Allergic sensitization in childhood, especially in early childhood and especially to food allergens, is critical and of highest interest as development of an “allergic phenotype” or “atopy” has been shown to facilitate subsequent sensitization to other allergens. Hence allergies in childhood can be the first step of an allergic cascade leading to multiple allergies later in life, a process commonly referred to as “The Atopic March”. For example, it has been demonstrated in human cohorts that children with persistent food hypersensitivity early in life have a dramatically increased risk to develop allergic rhinitis (hay fever) or asthma later in childhood (Ostblöm et al 2008). Children with milder forms of food hypersensitivity also have increased risk for development of respiratory allergies but to a lesser degree than children with persistent food hypersensitivity. Therefore, attenuating the severity of food hypersensitivity may be crucial for slowing down the “Atopic March”. In this context the management of allergic episodes and prevention of allergies are, in childhood and infancy, of the highest importance.
The immune system of infants is actively developing all along the few first years of life. Acting on, preventing, avoiding, managing, reducing or modulating the allergic reactions in such young patients can influence their allergic profile short term but also longer term for later in life.
Prevention of Allergies Can be Achieved on Different Levels:
“Primary prevention” is the effect of preventing or reducing the risk of sensitization of patients to allergens, characterized by absence or reduced levels of allergen-specific IgE antibodies. Preventing or reducing sensitization will result in absence or reduction of allergic symptoms upon exposure to the same allergen. By modulating the way a patient gets sensitized in regard to one allergen or one group of allergens (primary prevention), the subsequent allergic response may also be modulated.
“Secondary prevention” is the effect of modulating the symptoms of allergies, i.e. the occurrence or intensity of the allergic reaction in patient already sensitized to one or several allergens when the patient is re-exposed to said allergen(s). By modulating the occurrence or intensity of the allergic symptoms (secondary prevention), the inconvenience associated with allergies is minimized.
Given these distinct concepts of allergy prevention it may be hypothesized that by virtue of their inherent mechanisms of action, some compounds might act solely at one or at both of these specific levels of prevention. Some may, for example, solely reduce the sensitization to a specific allergen (primary prevention), while other compounds may solely have an effect on the secondary prevention and reduce the severity of allergic reactions. Other compounds may be able to influence both sensitization and symptoms and thus are effective in promoting primary and secondary prevention.
Food allergens are among the first allergens that infants encounter in their early life: typically, cow's milk proteins may be encountered by infants not receiving exclusive breast-feeding. Milk-proteins are indeed among the most frequently observed causes for food allergy in infancy, followed by eggs and wheat proteins. In general, food allergies can manifest by cutaneous (rash, eczema, others) and gastrointestinal symptoms (abdominal cramps; pain, especially in the abdomen; vomiting) in infants and young children. Further sensitization and episodes of allergies can also appear when the infant/young child is exposed to a novel food such as cereals, vegetables, fruits, nuts or fish.
Strains of Bifidobacterium longum (B. longum) have been describes to play an important role in the gut microbiota and to be associated with positive health effects: They are typically present at high numbers in the gut microbiota of healthy breast-fed infants. They can promote good digestion, boost the immune system, and produce lactic and acetic acid that controls intestinal pH. These bacteria can also inhibit the growth of Candida albicans, E. coli, and other bacteria with pathogenic characteristics. B. longum in general or specific strains of B. longum can be classified as probiotics according to the WHO definition.
To a certain extent specific strains of B. longum have been described to have an antiallergenic effect For example, patients suffering from allergic rhinitis due to Japanese cedar pollinosis showed reduced allergic symptoms after consumption of B. longum BB536 for several weeks before and during the pollen season (Xiao J Z, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N, Miyaji K, Iwatsuki K, Togashi H, Enomoto K, Enomoto T. Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial. Clin Exp Allergy. 2006 November; 36(11):1425-35. Xiao J Z, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N, Iwatsuki K, Kokubo S, Togashi H, Enomoto K, Enomoto T. Effect of probiotic Bifidobacterium longum BB536 [corrected] in relieving clinical symptoms and modulating plasma cytokine levels of Japanese cedar pollinosis during the pollen season. A randomized double-blind, placebo-controlled trial. J Investig Allergol Clin Immunol. 2006; 16(2):86-93.)
Furthermore various probiotic cultures or mixes of probiotics have been described for their effect on the allergic immune system: for example EP1858336 (WO2006697949), describes a mix of probiotics that can decrease the risk of allergies due to wheat flour albumin and globulins. JP2006028050 describes the skin allergy suppressive properties of compositions comprising probiotic bacteria such as Lactobacillus and Streptococcus. WO2009072889, by Jan knoll et al, describes a Bifidobacterium that can be used in improving the lung function of subjects suffering from dust mite allergy.
JP10309178 suggests how a human-originated Bifidobacterium may help in curing food allergy or in inducing peroral immune tolerance.
However there remains a need for specifically reducing allergic reactions and symptoms in the population of young children and infants. This is especially important when considering the maturation of both the intestinal and immune systems undergoing in young children and when considering the multiplicity of novel allergens that the young children are exposed to, especially around weaning.
The question of food born allergic reactions in the young age is even further complicated by the specific nutritional needs of infants and young children. Caloric intake, caloric density, variety of desirable nutrient, protein content and protein quality are all among the factors important to bring the most appropriate nutrition to infants and young children. The presence of micronutrients such as vitamins and minerals are also of importance, more specifically when their concentration is limited by specific recommended ranges corresponding to the age of the target patients. As such, for the young children and infants, the matrices of food delivery are inherently complex but they are also of less variety: for example infants, although potentially allergic, usually require a specific protein balance in a matrix of milk-derived proteins. The presence of such multiple nutrients can potentiate the effect of the food allergens. In such complex matrices, low key food allergens unable to trigger allergic manifestation alone can then become more powerful at initiating an allergic reaction. Similarly compounds that may neutralize allergens or act on allergy prevention may see their effect diminished or annihilated in such complex nutritional matrices. Specifically it is not predictable whether compounds usually recognized to act on allergy prevention would still be active, and to which extend, in complex matrices such as nutritional composition for infants or young children.
There is a need to bring relief in the symptoms of food allergies in populations of infants and young children that have a history of allergic episodes and/or are allergic.
There is a need to provide a complete nutritional composition that not only brings a variety of nutrients but also reduces the severity of allergic reactions.
There is a need for providing a nutritional composition modulating the allergic reaction of young patients suffering from light to moderate forms of allergies, as these patients have special needs dictated by the incomplete maturity of their intestinal and immune systems.
There is also a need for modulating allergic reactions in young children that do not tolerate stringent pharmaceutical molecules, for example by nutritional interventions such as including modulators of the immune system into the regular nutritional regimen.
There is a need for providing a nutritional composition modulating the allergic reaction of young patients at the time, and around the time of weaning when the intestinal tract undergoes substantial modification and when new solid foods, potentially containing new allergenic proteins, are introduced and hence the patient is particularly susceptible to the sensitization to food allergens.
There is a need for alleviating the symptoms of allergies by providing an effective composition, possibly by reducing the exposure to intact allergens, even though the composition may not directly reduce the sensitization to allergens.
There is a need for a composition that has a positive effect on secondary prevention of allergy while not necessarily acting on the primary prevention to the same allergies.
There is finally a need for a composition, most particularly suited for young patients that by reduction of symptoms can help to diminish the “allergic phenotype” and thus can lower sensitization later in life to new allergens. There is a need for attenuating the atopic march.